A Phase 2 Study of Belzutifan (PT2977, MK-6482) for the Treatment of Von Hippel Lindau (VHL) Disease-Associated Renal Cell Carcinoma (RCC) (MK-6482-004)

NCT03401788 | Active Not Recruiting Phase 2 FDA Drug

• 6 other identifiers: 6482-004PT2977-202MK-6482-0042023-509119-99-00U1111-1309-60632018-000125-30
• Study Type: interventional
• Target: 50
• Locations: 4 countries
• Sites: 11

Brief Summary

This study is designed to investigate belzutifan as a treatment for VHL disease associated RCC.

Conditions

VHL - Von Hippel-Lindau Syndrome; VHL Gene Mutation; VHL Syndrome; VHL Gene Inactivation; VHL-Associated Renal Cell Carcinoma; VHL-Associated Clear Cell Renal Cell Carcinoma

Keywords

VHL

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) in VHL Disease-Associated RCC Tumors

  ORR is defined as the percentage of participants in the analysis population who have a best confirmed response of Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR will be assessed by independent review committee (ICR) for the primary analysis.

  Up to approximately 4 years

Secondary Outcomes (13)

• Duration of Response (DOR) in VHL Disease-Associated RCC Tumors

  Up to approximately 4 years

• Time to Response (TTR) in VHL Disease-Associated RCC Tumors

  Up to approximately 4 years

• Progression-free Survival (PFS) in VHL Disease-Associated RCC Tumors

  Up to approximately 4 years

• Time to Surgery (TTS) in VHL Disease-Associated RCC Tumors

  Up to approximately 4 years

• ORR in VHL Disease-Associated Non-RCC Tumors

  Up to approximately 4 years

Study Arms (1)

Open Label Belzutifan

EXPERIMENTAL

Participants receive 120 mg belzutifan orally once daily. Participants may continue to receive belzutifan in the absence of unacceptable treatment related toxicity or unequivocal disease progression.

Drug: Belzutifan

Interventions

Belzutifan DRUG

120 mg once daily (three 40 mg oral tablets once daily).

Also known as: PT2977, MK-6482, WELIREG™

Open Label Belzutifan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a diagnosis of von Hippel Lindau disease, based on a germline VHL alteration
• Has at least 1 measurable solid RCC tumor and no RCC tumor that requires immediate surgical intervention. The diagnosis of RCC can be radiologic (histologic diagnosis not required). Participants may have VHL disease-associated tumors in other organ systems

You may not qualify if:

• Has received prior treatment with belzutifan or another HIF-2α inhibitor
• Has had any systemic anti-cancer therapy (includes anti-vascular endothelial growth factor \[VEGF\] therapy or any systemic investigational anti-cancer agent)
• Has an immediate need for surgical intervention for tumor treatment
• Has evidence of metastatic disease on screening imaging

Sponsors & Collaborators

• Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (11)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Aarhus University Hospital

Aarhus, Denmark

Location

Hospital Georges Pompidou

Paris, France

Location

Cambridge University Hospital

Cambridge, United Kingdom

Location

Related Publications (3)

• Iliopoulos O, Iversen AB, Narayan V, Maughan BL, Beckermann KE, Oudard S, Else T, Maranchie JK, Goldberg CM, Fu W, Perini RF, Liu Y, Linehan WM, Srinivasan R, Jonasch E. Belzutifan for patients with von Hippel-Lindau disease-associated CNS haemangioblastomas (LITESPARK-004): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2024 Oct;25(10):1325-1336. doi: 10.1016/S1470-2045(24)00389-9. Epub 2024 Sep 13.

  PMID: 39284337 RESULT

• Srinivasan R, Iliopoulos O, Beckermann KE, Narayan V, Maughan BL, Oudard S, Else T, Maranchie JK, Iversen AB, Cornell J, Perini RF, Liu Y, Linehan WM, Jonasch E. Belzutifan for von Hippel-Lindau disease-associated renal cell carcinoma and other neoplasms (LITESPARK-004): 50 months follow-up from a single-arm, phase 2 study. Lancet Oncol. 2025 May;26(5):571-582. doi: 10.1016/S1470-2045(25)00099-3. Epub 2025 Apr 12. Erratum In: Lancet Oncol. 2025 Jul;26(7):e349. doi: 10.1016/S1470-2045(25)00354-7.

  PMID: 40228516 DERIVED

• Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425.

  PMID: 34818478 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

von Hippel-Lindau Disease

Interventions

belzutifan

Condition Hierarchy (Ancestors)

Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 2 Open Label

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 17, 2018
• Study Start: May 2, 2018
• Primary Completion (Estimated): April 29, 2027
• Study Completion (Estimated): April 29, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (8); GB (1); FR (1); DK (1)